Thyroid hormone excess can cause bone loss and may be a potential risk factor for secondary osteoporosis for large numbers of the population. Menopause may aggravate these effects of thyroid hormones. Although the relationship between thyroid hormones and bone metabolism has been well documented, the mechanism of action of these hormones on bone has not yet been fully elucidated. Since there is a well-defined relationship between the immune system and thyroid hormones, suggesting that thyroid hormones stimulate the production of cytokines by immune cells. Thyroid hormones might stimulate the synthesis of these factors in other tissues, as well, resulting in elevated serum levels of the cytokines. A number of cytokines play important roles in the regulation of bone metabolism. Therefore, we postulate that certain cytokines participate in the mediation of thyroid hormone effects on bone. In the proposed study, we plan to investigate the changes in the circulating levels of cytokines involved in bone metabolism, including interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and insulin-like growth factor I (IFG-I). A total of 90 subjects will be examined including pre- and postmenopausal healthy women and men, as well as patients with hyper- and hypothyroidism before and after treatment. Bone biochemical parameters, including serum osteocalcin and urinary hydroxyproline excretion, bone mineral content, using single and dual photon absorptiometry, and IL-1alpha and beta secretion by monocyte cultures isolated from patients' blood will also be measured before and after treatment. Serum bone resorbing activity (SBRA) of sera showing high and low cytokine levels will be determined in fetal rat limb bone cultures. Data will be analyzed in order to determine whether there are correlations between the effects of thyroid hormones on the production of cytokines and bone metabolism.